1. Field of the Invention
The present invention relates generally to cobalt-porphyrin complexes which are useful as anti-obesity agents, as well as to compounds, compositions and methods related to the same.
2. Description of the Related Art
Porphine i is the parent substance of porphyrins, a group of compounds found in all living matter and which are the basis of respiratory pigments in animals and plants. Porphyrins constitute a class of compounds wherein the hydrogen atoms of porphine's pyrrole rings are substituted with various side chains. Porphyrins have received extensive study, much of which is presented in a multi-volume treatise entitled The Porphyrins, D. Dolphin, Ed., Academic Press, N.Y., 1978. 
An exemplary porphyrin is protoporphyrin IX ii. Protoporphyrin IX is the immediate precursor of heme, which is the complex formed upon chelation of iron by protophorphryin. In addition to iron, protoporphryin IX readily chelates with other metals. When chelated to cobalt, the resulting complex is cobalt-protoporphyrin iii (including salts and/or ligand complexes thereof). 
A related analogue of protoporphyrin IX ii is mesoporphyrin iv, which differs from protoporphyrin to the extent that the two ethylene side chains are fully saturated. When chelated to cobalt, cobalt mesoporphyrin v results (including salts and/or ligand complexes thereof). 
Cobalt protoporphyrin (“Co-PP”) has been reported to regulate food intake and body weight in rats (Galbraith and Kappas, Proc. Natl. Acad Sci. U.S.A. 86:7653-7657, 1989), as well as in other animals such as rats, dogs and monkeys. A single subcutaneous injection of Co-PP produces a prompt dose-dependent decrease in food intake in Sprague Dawley rats. This result is accompanied by a sustained decrease in body weight, that is characterized by decreases in carcass fat content without changes in protein content. Smaller doses of Co-PP delivered by intracerebroventricular administration has also been found to elicit the same effect.
The regulatory effect of Co-PP has also been extended to animals that are genetically destined to become markedly obese. Thus, subcutaneous administration of Co-PP to Zucker rats whose obesity is conferred by homozygosity of the fa gene (fa/fa) produces long-sustained reduction in body weight (Galbraith and Kappas, Pharmacology 41:292-298, 1990). The effect of Co-PP is profound and believed to be caused by the phenotype of gene expression in the fa/fa animal to revert to a phenotype similar to that of the heterozygous lean animal. Whereas cobalt mesoporphyrin (“Co-MP”) has a comparable biological profile, the same effect is not found upon administration of inorganic cobalt, or a number of other metal chelates of porphyrins. The mechanism of action of Co-PP for regulation of body weight is unknown, and it has been shown that the weight loss in rats is not mediated by the neuropeptide Y system (Choi et al, Brain Research 729:223-227, 1996; Turner et al, Physiology and Behavior 56:10009-1014, 1994).
Administration of Co-PP and/or Co-MP for regulation of body weight is not without drawbacks. For example, oxidative stress has been associated with administration of high doses of Co-PP (see Tomaro et al., Arch. Biochem. Biophys. 286:610-617, 1991). Accordingly, there is a need in the art for compounds which have the beneficial properties associated with Co-PP and/or Co-MP, such as the ability to regulate body weight, but which not possess the unwanted side-effects presently encountered with administration of the same. The present invention fulfills these needs and provides other related advantages.